In schistosomiasis the parasite egg is crucial in both pathogenesis and transmission, but schistosome reproductive biology is poorly understood. The overall aim of this project is understanding of the events and processes necessary for successful pairing, maturation, vitellogenesis, and oviposition in schistosomes. Such knowledge will help develop methods to frustrate egg production, thereby minimizing and controlling the disease. A more specific goal is to identify and characterize the conditions for attaining and maintaining sexual maturity in female worms. By comparison and analogy with related flatworms and other invertebrates, and on the basis of our preliminary studies it is probable that neurosecretory hormones play an active role in reproductive development of these organisms. Comparisons will be made between female S. mansoni, which remain very immature; S. mattheei, which develop partly; and Schistosomatium douthitti, which mature fully in unisexual infections. We will study reproductive and neuronal components and their interconnections in mammalian and in vitro stages of these three females, including unisexual, paired, and regressing (formerly paired) worms. Reciprocal crosses will be made to see why S. mansoni males will cause S. mattheei females to produce viable eggs, but the reverse cross is unproductive. Analyses will be conducted by histochemical and immunocytochemical means, with identification and characterization of neurosecretory cells and granules, with and without microtubule inhibitors. Neuropeptides will be extracted, identified and quantitated by radioimmunoassay, and certain hormone receptors by radioreceptor assays. Another specific goal is to understand the relatioships between host environment and worm sexual development, especially hermaphroditism in male worms and inhibition of females in guinea pigs. Special attention will be given to gut hormones, particularly insulin which in guinea pigs is very different from that of all other mammals. Worms will be cultured with gut extracts and with insulin from guinea pig, mouse, or hamster, and evaluated for feminizataion and hermaphroditism.